chr16-58186853-C-G

Position:

• chr16-58186853-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001896.4(CSNK2A2):​c.220G>C​(p.Val74Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CSNK2A2 NM_001896.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.90

Genes affected

CSNK2A2 (HGNC:2459): (casein kinase 2 alpha 2) This gene encodes the alpha', or alpha 2, catalytic subunit of the protein kinase enzyme, casein kinase 2 (CK2). Casein kinase 2 is a serine/threonine protein kinase that phosphorylates acidic proteins such as casein. It is involved in various cellular processes, including cell cycle control, apoptosis, and circadian rhythms. This heterotetrameric kinase includes two catalytic subunits, either alpha or alpha', and two regulatory beta subunits. The closely related gene paralog encoding the alpha, or alpha 1 subunit (CSNK2A1, Gene ID: 1457) is found on chromosome 20. An intronic variant in this gene (alpha 2) may be associated with leukocyte telomere length in a South Asian population. A related transcribed pseudogene is found on chromosome 11. [provided by RefSeq, Aug 2017]

CSNK2A2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41974175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSNK2A2	NM_001896.4	c.220G>C	p.Val74Leu	missense_variant	3/12	ENST00000262506.8	NP_001887.1
CSNK2A2	XM_047433626.1	c.220G>C	p.Val74Leu	missense_variant	3/11		XP_047289582.1
CSNK2A2	XM_005255801.4	c.-191-1G>C		splice_acceptor_variant, intron_variant			XP_005255858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSNK2A2	ENST00000262506.8	c.220G>C	p.Val74Leu	missense_variant	3/12	1	NM_001896.4	ENSP00000262506.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 28, 2023

The c.220G>C (p.V74L) alteration is located in exon 3 (coding exon 3) of the CSNK2A2 gene. This alteration results from a G to C substitution at nucleotide position 220, causing the valine (V) at amino acid position 74 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.0051	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.99	D;T;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.87	L;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.6	D;.;D
REVEL	Benign	0.17
Sift	Uncertain	0.0080	D;.;D
Sift4G	Uncertain	0.057	T;D;D
Polyphen		0.031	B;.;.
Vest4		0.55
MutPred		0.51		Gain of glycosylation at P73 (P = 0.0954);.;Gain of glycosylation at P73 (P = 0.0954);
MVP		0.41
MPC		1.5
ClinPred		0.89	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-58220757;